Patients with chest pain syndromes may develop left ventricular dysfunction over time, even if coronary arteries appear normal and there is no evidence of cardiomyopathy. Because hyperinsulinemia has been reported in patients with chest pain and normal coronary angiograms and because insulin has been shown to be capable of stimulating a variety of cell lines, we investigated the possibility that hyperinsulinemia might cause progressive left ventricular dysfunction in this patient population, who have myocardial fibrosis on biopsy. We assessed left ventricular function by radionuclide angiography and insulin responses to an oral glucose load in 76 patients with chest pain, normal EKGs, and normal coronary angiograms. All patients were non-diabetic. Compared to 26 controls of similar age, gender, and body mass, patients had a higher peak insulin response to glucose load (145+69 vs. 102+44 microU/ml, p<0.01) and sum of insulin values at 30, 60, 90, 120, and 180 minutes after glucose load (480+229 vs. 312+128 microU/ml, p<0.001). The resting left ventricular ejection fractions ranged from 33% to 75% (average 50+9%) and was inversely related to the log of the peak insulin (r= -.301, p<0.01) and the log of the insulin sum (r= -.322, p<0.005). The 12 patients with resting abnormal wall motion had higher insulin sums (613+244 microU/ml) than the 64 patients with normal rest left ventricular function (456+227 microU/ml, p<0.05). No correlation existed between the insulin response to glucose and age or the left ventricular ejection response to exercise, or between the resting left ventricular ejection fraction and age. Thus, an excess insulin response to glucose load is common in patients with chest pain and normal coronary angiograms and appears to be associated with abnormal resting left ventricular systolic function. A causal relationship of hyperinsulinemia to progressive left ventricular dysfunction remains to be defined.